Correction: Performance of risk prediction scores for cardiovascular mortality in older persons: External validation of the SCORE OP and appraisal

[This corrects the article DOI: 10.1371/journal.pone.0231097.

Promising results of a clinical feasibility study: CIRBP as a potential biomarker in pediatric cardiac surgery

ObjectiveCold-inducible RNA binding Protein (CIRBP) has been shown to be a potent inflammatory mediator and could serve as a novel biomarker for inflammation. Systemic inflammatory response syndrome (SIRS) and capillary leak syndrome (CLS) are frequent complications after pediatric cardiac surgery increasing morbidity, therefore early diagnosis and therapy is crucial. As CIRBP serum levels have not been analyzed in a pediatric population, we conducted a clinical feasibility establishing a customized magnetic bead panel analyzing CIRBP in pediatric patients undergoing cardiac surgery.MethodsA prospective hypothesis generating observational clinical study was conducted at the German Heart Center Berlin during a period of 9 months starting in May 2020 (DRKS00020885, https://drks.de/search/de/trial/DRKS00020885). Serum samples were obtained before the cardiac operation, upon arrival at the pediatric intensive care unit, 6 and 24 h after the operation in patients up to 18 years of age with congenital heart disease (CHD). Customized multiplex magnetic bead-based immunoassay panels were developed to analyze CIRBP, Interleukin-1β (IL-1β), Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-10 (IL-10), Monocyte chemotactic protein 1 (MCP-1), Syndecan-1 (SDC-1), Thrombomodulin (TM), Vascular endothelial growth factor (VEGF-A), Angiopoietin-2 (Ang-2), and Fibroblast growth factor 23 (FGF-23) in 25 µl serum using the Luminex MagPix® system.Results19 patients representing a broad range of CHD (10 male patients, median age 2 years, 9 female patients, median age 3 years) were included in the feasibility study. CIRBP was detectable in the whole patient cohort. Relative to individual baseline values, CIRBP concentrations increased 6 h after operation and returned to baseline levels over time. IL-6, IL-8, IL-10, and MCP-1 concentrations were significantly increased after operation and except for MCP-1 concentrations stayed upregulated over time. SDC-1, TM, Ang-2, as well as FGF-23 concentrations were also significantly increased, whereas VEGF-A concentration was significantly decreased after surgery.DiscussionUsing customized magnetic bead panels, we were able to detect CIRBP in a minimal serum volume (25 µl) in all enrolled patients. To our knowledge this is the first clinical study to assess CIRBP serum concentrations in a pediatric population

Self-reported medication in community-dwelling older adults in Germany: results from the Berlin Initiative Study

Background: Older adults have the highest drug utilization due to multimorbidity. Although the number of people over age 70 is expected to double within the next decades, population-based data on their medication patterns are scarce especially in combination with polypharmacy and potentially inappropriate medication (PIM). Our objective was to analyse the frequency of polypharmacy, pattern of prescription (PD) and over-the-counter (OTC) drug usage, and PIMs according to age and gender in a population-based cohort of very old adults in Germany. Methods: Cross-sectional baseline data of the Berlin Initiative Study, a prospective cohort study of community-dwelling adults aged ≥70 years with a standardized interview including demographics, lifestyle variables, co-morbidities, and medication assessment were analysed. Medication data were coded using the Anatomical Therapeutic Chemical (ATC) classification. Age- and sex-standardized descriptive analysis of polypharmacy (≥5 drugs, PD and OTC vs. PD only and regular and on demand drugs vs regular only), medication frequency and distribution, including PIMs, was performed by age (</≥80) and gender. Results: Of 2069 participants with an average age of 79.5 years, 97% (95%CI [96%;98%]) took at least one drug and on average 6.2 drugs (SD = 3.5) with about 40 to 66% fulfilling the criteria of polypharmacy depending on the definition. Regarding drug type more female participants took a combination of PD and OTC (male: 68%, 95%CI [65%;72%]); female: 78%, 95%CI [76%;80%]). Most frequently used were drugs for cardiovascular diseases (85%, 95%CI [83%;86%]). Medication frequency increased among participants aged ≥80 years, especially for cardiovascular drugs, antithrombotics, psychoanaleptics and dietary supplements. Among the top ten prescription drugs were mainly cardiovascular drugs including lipid-lowering agents (simvastatin), beta-blockers (metoprolol, bisoprolol) and ACE inhibitors (ramipril). The most common OTC drug was acetylsalicylic acid (35%; 95%CI [33%;37%])). Dose-independent PIM were identified for 15% of the participants. Conclusions: Polypharmacy was excessive in older adults, with not only PD but also OTC drugs contributing to the high point prevalence. The medication patterns reflected the treatment of chronic diseases in this age group. There was even an increase in medication frequency between below and above 80 years especially for drugs of cardiovascular diseases, antithrombotic medication, psychoanaleptics, and dietary supplements

Nationwide Registry‐Based Analysis of Infective Endocarditis Risk After Pulmonary Valve Replacement

Background: Infective endocarditis (IE) after pulmonary valve replacements in congenital heart disease is a significant concern. This study aimed to identify specific long-term risk factors for IE after percutaneous pulmonary valve implantation or surgical pulmonary valve replacement. Methods and Results: All patients with congenital heart disease from the National Register for Congenital Heart Defects with at least 1 pulmonary valve replacement before January 2018 were included. A total of 1170 patients (56.3% men, median age at study inclusion 12 [interquartile range {Q1-Q3} 5-20 years]) received 1598 pulmonary valve replacements. IE occurred in 4.8% of patients during a follow-up of total 9397 patient-years (median 10 [Q1-Q3, 6-10] years per patient). After homograft implantation 7 of 558 (1.3%) patients developed IE, after heterograft implantation 31 of 723 (4.3%) patients, and after Melody valve implantation 18 of 241 (7.5%) patients. Edwards Sapien and mechanical valves were used less frequently and remained without IE. The incidence of IE in heterografts excluding Contegra valves was 7 of 278 (2.5%), whereas the incidence of IE in Contegra valves was 24 of 445 (5.4%). The risk of IE was not increased compared with homografts if Contegra valves were excluded from the heterografts (hazard ratio [HR], 2.60; P=0.075). The risk of IE was increased for bovine jugular vein valves, Contegra valves (HR, 6.72; P<0.001), and Melody valves (HR, 5.49; P<0.001), but did not differ between Melody valves and Contegra valves (HR, 1.01; P=0.978). Conclusions: Bovine jugular vein valves have the highest risk of IE, irrespective of the mode of deployment, either surgical or percutaneous

Medical treatment of pulmonary hypertension in adults with congenital heart disease : updated and extended results from the International COMPERA-CHD Registry

Funding Information: The authors are indebted to the COMPERA investigators and their staff. We explicitly thank Dr. Claudia S. Copeland for the professional editing of the final draft of the manuscript. Funding: COMPERA is funded by unrestricted grants from Acceleron, Actelion Pharmaceuticals (Janssen), Bayer, OMT and GSK. These companies were not involved in data analysis or the writing of this manuscript. Funding Information: ICMJE uniform disclosure form (available at https:// dx.doi.org/10.21037/cdt-21-351). The series “Current Management Aspects in Adult Congenital Heart Disease (ACHD): Part IV” was commissioned by the editorial office without any funding or sponsorship. Dr. DH reports non-financial support from Actelion, Boehringer-Ingelheim, and Shire, outside the submitted work; Dr. DP reports personal fees from Actelion, Biogen, Aspen, Bayer, Boehringer Ingelheim, Daiichi Sankyo, and Sanofi, outside the submitted work; Dr. MD reports personal fees from Actelion, Bayer, GSK and MSD, outside the submitted work; Dr. HAG reports personal fees from Actelion, Bayer, Gilead, GSK, MSD, Pfizer and United Therapeutics, outside the submitted work; Dr. MG reports personal fees from Actelion, Bayer and GSK, outside the submitted work; Dr. MMH reports personal fees from Acceleron, Actelion, Bayer, MSD and Pfizer, outside the submitted work; Dr. CDV reports personal fees from Actelion, Bayer, GSK, MSD, Pfizer, and United Therapeutics, outside the submitted work; Dr. RE reports personal fees from Actelion, Boehringer Ingelheim, OMT, Bayer, and Berlin Chemie; grants from Actelion and Boehringer Ingelheim, outside the submitted work; Dr. MH reports grants and personal fees from Actelion, personal fees from Bayer, Berlin Chemie, Boehringer Ingelheim, GSK, Janssen, Novartis and MSD, outside the submitted work; Dr. MH reports personal fees from Acceleron, Actelion, AstraZeneca, Bayer, BERLIN CHEMIE, GSK, MSD, Novartis and OMT, outside the submitted work; Dr. HW reports personal fees from Action, Bayer, Biotest, Boehringer, GSK, Pfizer, and Roche, outside the submitted work; Dr. DS reports personal fees from Actelion, Bayer, and GSK, outside the submitted work; Dr. LS reports personal fees from Actelion, Bayer, and MSD, outside the submitted work; Dr. SU reports grants from Swiss National Science Foundation, Zurich Lung, Swiss Lung, and Orpha Swiss, grants and personal fees from Actelion SA/Johnson & Johnson, Switzerland, and MSD Switzerland, outside the submitted work; Dr. TJL reports personal fees from Actelion, Janssen-Cilag, BMS, MSD, and OMT GmbH, outside the submitted work; Dr. LB reports personal fees from Actelion, outside the submitted work; Dr. MC reports personal fees from Boehringer Ingelheim Pharma GmbH, Roche Pharma, and Boehringer Ingelheim, outside the submitted work; Dr. HW reports personal fees from Boehringer Ingelheim, and Roche, outside the submitted work. Dr. EG reports personal fees from Actelion, Janssen, Bayer, MSD, Bial, OrPha Swiss GmbH, OMT and Medscape, outside the submitted work; Dr. SR reports personal fees from Actelion, Bayer, GSK, Pfizer, Novartis, Gilead, MSD, and United Therapeutics, outside the submitted work. The authors have no other conflicts of interest to declare. Publisher Copyright: © Cardiovascular Diagnosis and Therapy. All rights reserved.Background: Pulmonary arterial hypertension (PAH) is common in congenital heart disease (CHD). Because clinical-trial data on PAH associated with CHD (PAH-CHD) remain limited, registry data on the long-term course are essential. This analysis aimed to update information from the COMPERA-CHD registry on management strategies based on real-world data. Methods: The prospective international pulmonary hypertension registry COMPERA has since 2007 enrolled more than 10,000 patients. COMPERA-CHD is a sub-registry for patients with PAH-CHD Results: A total of 769 patients with PAH-CHD from 62 specialized centers in 12 countries were included into COMPERA-CHD from January 2007 through September 2020. At the last follow-up in 09/2020, patients [mean age 45.3±16.8 years; 512 (66%) female] had either post-tricuspid shunts (n=359; 46.7%), pre-tricuspid shunts (n=249; 32.4%), complex CHD (n=132; 17.2%), congenital left heart or aortic valve or aortic disease (n=9; 1.3%), or miscellaneous CHD (n=20; 2.6%). The mean 6-minute walking distance was 369±121 m, and 28.2%, 56.0%, and 3.8% were in WHO functional class I/II, III or IV, respectively (12.0% unknown). Compared with the previously published COMPERA-CHD data, after 21 months of followup, the number of included PAH-CHD patients increased by 91 (13.4%). Within this group the number of Eisenmenger patients rose by 39 (16.3%), the number of “Non-Eisenmenger PAH” patients by 45 (26.9%). Currently, among the 674 patients from the PAH-CHD group with at least one follow-up, 450 (66.8%) received endothelin receptor antagonists (ERA), 416 (61.7%) PDE-5 inhibitors, 85 (12.6%) prostacyclin analogues, and 36 (5.3%) the sGC stimulator riociguat. While at first inclusion in the COMPERA-CHD registry, treatment was predominantly monotherapy (69.3%), this has shifted to favoring combination therapy in the current group (53%). For the first time, the nature, frequency, and treatment of significant comorbidities requiring supportive care and medication are described. Conclusions: Analyzing “real life data” from the international COMPERA-CHD registry, we present a comprehensive overview about current management modalities and treatment concepts in PAH-CHD. There was an trend towards more aggressive treatment strategies and combination therapies. In the future, particular attention must be directed to the “Non-Eisenmenger PAH” group and to patients with complex CHD, including Fontan patients.publishersversionPeer reviewe

Pulmonary Hypertension in Adults with Congenital Heart Disease: Real-World Data from the International COMPERA-CHD Registry

Introduction: Pulmonary hypertension (PH) is a common complication in patients with congenital heart disease (CHD), aggravating the natural, post-operative, or post-interventional course of the underlying anomaly. The various CHDs differ substantially in characteristics, functionality, and clinical outcomes among each other and compared with other diseases with pulmonary hypertension. Objective: To describe current management strategies and outcomes for adults with PH in relation to different types of CHD based on real-world data. Methods and results: COMPERA (Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension) is a prospective, international PH registry comprising, at the time of data analysis, >8200 patients with various forms of PH. Here, we analyzed a subgroup of 680 patients with PH due to CHD, who were included between 2007 and 2018 in 49 specialized centers for PH and/or CHD located in 11 European countries. At enrollment, the patients’ median age was 44 years (67% female), and patients had either pre-tricuspid shunts, post-tricuspid shunts, complex CHD, congenital left heart or aortic disease, or miscellaneous other types of CHD. Upon inclusion, targeted therapies for pulmonary arterial hypertension (PAH) included endothelin receptor antagonists, PDE-5 inhibitors, prostacyclin analogues, and soluble guanylate cyclase stimulators. Eighty patients with Eisenmenger syndrome were treatment-naïve. While at inclusion the primary PAH treatment for the cohort was monotherapy (70% of patients), with 30% of the patients on combination therapy, after a median observation time of 45.3 months, the number of patients on combination therapy had increased significantly, to 50%. The use of oral anticoagulants or antiplatelets was dependent on the underlying diagnosis or comorbidities. In the entire COMPERA-CHD cohort, after follow-up and receiving targeted PAH therapy (n = 511), 91 patients died over the course of a 5-year follow up. The 5-year Kaplan–Meier survival estimate for CHD associated PH was significantly better than that for idiopathic PAH (76% vs. 54%; p < 0.001). Within the CHD associated PH group, survival estimates differed particularly depending on the underlying diagnosis and treatment status. Conclusions: In COMPERA-CHD, the overall survival of patients with CHD associated PH was dependent on the underlying diagnosis and treatment status, but was significantly better as than that for idiopathic PAH. Nevertheless, overall survival of patients with PAH due to CHD was still markedly reduced compared with survival of patients with other types of CHD, despite an increasing number of patients on PAH-targeted combination therapy

an analysis of data from the national database of the Regional Collaborative Arthritis Centres within the German Society of Rheumatology

Zielstellung: Für Patienten mit Rheumatoider Arthritis (RA) sollten I) klinische Merkmale und Behandlung von “young onset” RA (YORA) mit “late onset” RA (LORA) unter Berücksichtigung von Alter und Geschlecht verglichen, II) die neuen ACR/EULAR-Remissions-kriterien im Vergleich zur DAS28-Remission in unselektierten Routinepatienten evaluiert und III) die Veränderungen der Kosten zwischen 2002 und 2011 für Patienten im Erwerbs- und Rentenalter abgeschätzt werden. Methodik: Alle Analysen basieren auf RA-Patienten der Kerndokumentation der Regionalen Kooperativen Rheumazentren. I) 9.541 Patienten wurden nach Alter bei Krankheitsbeginn in YORA und LORA stratifiziert (Alters-Cut-off 65) und mit getrennten matched-pairs-Analysen verglichen. II) Für 6.864 Patienten wurde Remission nach 3 verschiedenen Kriterien berechnet. Mit logistischer Regression wurden Faktoren identifiziert, die die Nichterfüllung der neuen ACR/EULAR-Kriterien vorhersagen. III) Für die Jahre 2002 bis 2011 mit etwa 3.400 Patienten pro Jahr wurden Kosten mit festen als auch jährlich aktualisierten Preisen berechnet, für die Bestimmung der indirekten Kosten wurden Humankapital- und Friktionskostenansätze angewendet. Ergebnisse: I) Bei gleichem Alter hatten YORA-Patienten eine höhere Krankheitslast und berichteten unabhängig von Alter oder Krankheitsdauer häufiger Schlafstörungen und Fatigue. LORA-Patienten erhielten weniger synthetische oder biologische DMARDs. II) Von allen Patienten waren 28% in DAS28-, 7% in Boolescher und 11% in SDAI-Remission. Bei Patienten in DAS28-Remission waren hoher Schmerz und Fatigue, begleitende Wirbelsäulenerkrankun-gen, längere Krankheitsdauer und männliches Geschlecht prädiktiv für die Nichterfüllung der neuen Kriterien. III) Aufgrund der zunehmenden Biologikaverordnungen stiegen die direkten Kosten zwischen 2002 und 2011 deutlich, während die Ausgaben für Krankenhausaufenthalte und indirekte Kosten durch Arbeitsunfähigkeitszeiten und Erwerbsunfähigkeit zurückgingen. Schlussfolgerung: I) Eher die Dauer der RA als das Alter erklärt die differierende Krankheitslast zwischen YORA und LORA. Niedrige Verordnungsraten von DMARDs, trotz geringer Remissionsraten, deuten auf Behandlungsdefizite bei älteren Patienten. II) Patienten in Remission nach den neuen Kriterien tendieren nicht nur frei von aktiver RA sondern auch frei von anderen einschränkenden Erkrankungen zu sein. III) Die gestiegenen Behandlungskosten im letzten Jahrzehnt konnten teilweise durch Einsparungen bei stationären und indirekten Kosten ausgeglichen werden. Da die Therapiekosten seit 2009 stagnieren, wird kein weiterer relevanter Anstieg der Gesamtkosten erwartet.Objective: For patients with rheumatoid arthritis (RA), the aim was I) To compare clinical features and treatment of young onset RA (YORA) to late onset RA (LORA) accounting for differences in age and disease duration; II) To evaluate the performance of the new ACR/EULAR remission criteria compared to DAS28 remission in unselected real-life patients; III) To estimate the changes in direct and indirect costs between 2002 and 2011 for patients at working and at retirement age. Methods: All analyses are based on patients enrolled in the national database of the German Collaborative Arthritis Centres. I) 9,541 RA patients were stratified by age at disease onset to YORA and LORA (cut-off age 65). Two separate matched pairs analyses were performed. II) Remission was calculated according to three different criteria for 6,864 patients. Logistic regression analyses identified factors that predicted missing the new ACR/EULAR criteria. III) For the years 2002 to 2011 with about 3,400 patients each year costs were calculated using fixed prices as well as annually updated cost factors, for indirect costs using the human capital and the friction cost approaches. Results: I) At identical age, YORA patients had higher disease burden. Independent of age or disease duration, YORA patients reported more sleep disorders and fatigue. LORA patients received fewer synthetic or biologic DMARDs. II) Of all patients, 28% were in DAS28, 7% in Boolean and 11% in SDAI remission. For those in DAS28 remission, higher scores for pain and fatigue, the presence of degenerative spine disease, longer disease duration and male gender were predictive for missing the new criteria. III) Due to rising prescriptions of biologic agents, direct costs considerably increased between 2002 and 2011, while expenses due to inpatient treatment, sick leave and work disability decreased. Conclusion: I) Duration of RA, rather than age, explains differences in disease burden between YORA and LORA. The lower prescription rates of synthetic and biologic DMARDs, despite lower remission rates, indicate a potential treatment deficit in older patients. II) Patients fulfilling the new remission criteria tend to be not only free from active RA but also from other disabling diseases. The impact of co-morbidity should be taken into account if applied in clinical practice. III) The increase in treatment costs over the last decade was partly offset by lower hospitalisation rates and indirect costs. Since the rise in drug costs stagnates since 2009, no further increase in total costs is expected